Identifying comorbidities and lifestyle factors contributing to the cognitive profile of early Parkinson's disease.

BACKGROUND: Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. METHODS: Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. RESULTS: Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p < 0.05) and cognitive stimulation (< 0.01). Cognitive performance was negatively associated with interleukin 2 (Il2) (p < 0.05), Il6 (p < 0.05), iron (p < 0.05), and homocysteine (p < 0.005) levels, and positively associated with vitamin B12 levels (p < 0.005). CONCLUSIONS: We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with PD.

Parkinson's Disease: Impulsivity Does Not Cause Impulse Control Disorders but Boosts Their Severity.

Introduction: Impulse control disorders (ICDs) are a common complication of Parkinson's disease (PD) receiving dopamine agonist (DAA) Impulsivity is considered an underlying mechanism but evidence of this relationship is scarce. To explore the relationship between impulsivity and the presence and severity of ICD in PD. Methods: Prospective cross-sectional study of consecutive PD outpatients. Patients with dementia or previously known ICDs were excluded. Two measures of impulsivity were assessed: Barratt Impulsiveness Scale (BIS-11) for impulsiveness trait (main exposure) and commission errors in the Continuous Performance Test (CE) for motor inhibition. Main outcomes were diagnosis of ICD based on a comprehensive clinical interview and severity of ICD based on the Questionnaire for Impulsive-Compulsive Disorders. Results: Of 100 patients (mean [SD] age, 67.2 [8.8], 54 male), 31 had ICD. Patients with ICDs were 5.3 years younger (p = 0.01), used more frequently dopamine agonist (p = 0.02), alcohol (p = 0.009) and tobacco (p = 0.02). They were not more impulsive on BIS-11 (56 vs. 58, p = 0.23, adjusted p = 0.46) and CE (p = 0.96). No relationship was found between dopaminergic medications and impulsivity or ICD severity. Among patients with ICD, impulsivity was correlated with ICD severity (BIS-11 r = 0.33, p = 0.001, adjusted p = 0.002, CE r = 0.53, p = 0.006). Multivariate regression analysis confirmed the independent predictive role of both measures. Conclusions: Impulsivity is not associated with increased prevalence of ICD in PD but it is strongly linked to ICD severity. When considering dopamine replacement therapy, assessment of impulsivity may be a useful approach to detect those patients at risk of severe forms of ICD.

Facial emotion recognition impairment in patients with Parkinson's disease and isolated apathy.

Apathy is a frequent feature of Parkinson's disease (PD), usually related with executive dysfunction. However, in a subgroup of PD patients apathy may represent the only or predominant neuropsychiatric feature. To understand the mechanisms underlying apathy in PD, we investigated emotional processing in PD patients with and without apathy and in healthy controls (HC), assessed by a facial emotion recognition task (FERT). We excluded PD patients with cognitive impairment, depression, other affective disturbances and previous surgery for PD. PD patients with apathy scored significantly worse in the FERT, performing worse in fear, anger, and sadness recognition. No differences, however, were found between nonapathetic PD patients and HC. These findings suggest the existence of a disruption of emotional-affective processing in cognitive preserved PD patients with apathy. To identify specific dysfunction of limbic structures in PD, patients with isolated apathy may have therapeutic and prognostic implications.

PDD-Short Screen: a brief cognitive test for screening dementia in Parkinson's disease.

The diagnosis of Parkinson's disease with dementia (PDD) is currently based on clinical criteria (DSM-IV, MDS-Task Force). In daily practice and research studies, these criteria still depend on the subjective impression of the examiner. Brief screening tests (BST) are helpful in identifying patients with PD with dementia, which can be difficult in patients with advanced PD. We aimed to develop a BST for PD, the PDD-Short Screen (PDD-SS), to accurately and quickly screen for PDD. In this prospective study, 70 patients with nondemented (age 73.8 +/- 4.4) and 32 demented (age 73.8 +/- 4.4) PD regularly attending a Movement Disorders Clinic were included. Diagnosis of dementia was based on DSM-IV criteria, CDR score >or=1, and PD-CRS total score

Cut-off score of the Mattis Dementia Rating Scale for screening dementia in Parkinson's disease.

The prevalence of dementia in Parkinson's disease (PD) is close to 30%, and its incidence is 4 to 6 times higher than in age-matched general population. PD with dementia (PDD) is mainly characterized by a predominant and progressive frontal-subcortical impairment. The Mattis Dementia Rating Scale (MDRS) is a commonly used screening test that sensitively measures the degree of frontal-subcortical defects. Although the MDRS has been validated as a screening test of cognitive dysfunction in nondemented PD patients (PD-ND), its utility for screening dementia in PD is unknown. In order to validate the MDRS for diagnosis of PDD it was prospectively administered to 92 PD patients (57 PD-ND, 35 PDD) fulfilling UK-PDSBB criteria. Dementia was diagnosed according to DSM-IV-TR and a Clinical Dementia Rating (CDR) scale score >or=1. Univariate, logistic regression, and ROC curve analysis were carried out to measure the discriminative power of MDRS in PDD. Regression analysis showed MDRS total scores to independently differentiate PD-ND from PDD (P < 0.001). Age and education did not predict the presence of dementia. ROC curve analysis showed a cut-off score of

Effects of pallidotomy and bilateral subthalamic stimulation on cognitive function in Parkinson disease. A controlled comparative study.

Unilateral pallidotomy and bilateral subthalamic deep brain stimulation (STN-DBS) for Parkinson's disease (PD) have demonstrated a positive effect on motor functions. However, further studies are needed of the unintended cognitive effects accompanying these new surgical procedures. We studied the consequences of unilateral pallidotomy and STN-DBS on cognitive function in a controlled comparative design. Sixteen consecutive PD patients were assessed before and 6 months after unilateral pallidotomy (n = 8) and bilateral STN-DBS (n = 8). The same assessments were performed in a control group of eight non-operated matched PD patients recruited from surgery candidates who refused operation. The neuropsychological battery consisted of test measuring memory, attention, arithmetic, problem solving and language, as well as visuospatial, executive and premotor functions. An analysis of variance (factors time and treatment) was applied. No statistically significant differences were found in the presurgical evaluation of clinical and demographic data for the three treatment groups. The controlled comparison between presurgical and postsurgical performance revealed no significant changes in the cognitive domains tested in the pallidotomy group. The STN-DBS group showed a selective significant worsening of semantic verbal fluency (p = 0.005). This controlled comparative study suggests that neither unilateral pallidotomy nor bilateral STN-DBS have global adverse cognitive consequences, but bilateral STN-DBS may cause a selective decrease in verbal fluency.

A double-blind crossover, placebo-controlled study of the adenosine A2A antagonist theophylline in Parkinson's disease.

Blockade of the adenosine A2A receptor potentiates the effects of levodopa in experimental animals and may offer a novel nondopaminergic target for drug therapy in Parkinson's disease (PD). Open-label trials suggest that the nonspecific adenosine antagonist theophylline improves parkinsonian symptoms and increases ON time in advanced patients with PD. In a double-blind, crossover, placebo-controlled trial, the authors investigated the ability of stable plasma levels of theophylline (between 10-20 microg/mL after 15 days of treatment) to modulate the long-duration response and the short-duration response of levodopa in 10 patients with PD. Although theophylline induced a longer duration of the effect of levodopa in all Unified Parkinson's Disease Rating Scale variables considered, including dyskinesias, maximal levodopa-induced improvement and the duration of the effect of levodopa did not differ significantly from placebo. Only the secondary variable "akinesia" showed a statistical tendency to a more prolonged beneficial response with theophylline during an acute levodopa test (short-duration response), and tremor worsened with theophylline during levodopa withdrawal (long-duration response). No differences were observed during the subacute course of study medication added to levodopa. During this exploratory study, the effects of theophylline were not strong enough to potentiate clearly the antiparkinsonian action of levodopa or to increase ON time in patients with advanced PD.